Our goal is to understand the organization and control of taste signaling i.e. how individual pathways involved in taste transduction function and interact with each other. In the longer term we would like to define the components and the organization required for taste responses and to help elucidate the logic of taste coding. Specifically we would like to know what receptors mediate sweet and bitter taste; how tastant specificity and taste discrimination are accomplished; what topographic organization exists in the various taste buds and papillae; and how the information is transmitted and encoded in the afferent nerves. We have focused on the isolation and characterization of genes encoding sweet, amino acid and bitter taste receptors that can be used to mark the cells, define the corresponding signaling pathways, dissect receptor specificity, generate topographic maps, and trace the respective neuronal connectivity circuits. We have identified and characterized two families of G-protein coupled receptors, T1Rs and T2Rs, that are expressed in distinct subsets of taste receptor cells and that include functionally validated sweet, amino acid and bitter taste receptors. We have developed a number of genetically engineered mouse lines that have had a major impact in our understanding of how sweet, bitter and umami taste are encoded at the periphey. During this reporting period our work has concentrated on generation and characterization of a number of trangenic and knockout mice including lines in which individual or multiple taste receptor genes have been knocked out or where receptors and other molecules are expressed in specific subsets of taste receptor cells. Analysis of these mice has included behavioral and electrophysiological experimental approaches and has provided explicit information about the nature of sweet and umami taste receptors as well as strong indications about how taste modalities are encoded at the periphery. The critical next steps in defining the logic of taste coding are to examine the connectivity pathways of cells tuned to respond to sweet, bitter and umami tastes as well as to begin to define the molecular basis of salty and sour taste.